Substrate rigidity regulates the formation and maintenance of tissues

Substrate rigidity regulates the formation and maintenance of tissues
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DOI:
10.1529/biophysj.105.070144
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发表时间:
2006-03-01
影响因子:
3.4
通讯作者:
Wang, YL
Wang, YL
中科院分区:
生物学3区
文献类型:
--
作者:
Guo, WH;Frey, MT;Wang, YL

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细胞形成组织的能力是生物学中最基本的问题之一。然而,目前还不清楚是什么触发细胞在组织中相互粘附,并在将一块组织种植在培养表面上后进行迁移。使用化学成分相同但柔韧性不同的基质,我们证明这一过程是由基质刚性控制的:在坚硬的基质上,细胞相互迁移并散布在表面上,而在柔软的基质上,它们融合形成组织样结构。不仅在成纤维细胞和上皮细胞系中观察到类似的行为,而且在新生大鼠心脏的外植体中也观察到类似的行为。软基质上的细胞压实涉及基质粘附力减弱和肌球蛋白 II 依赖性收缩力(促使细胞相互靠近)的结合。我们的结果表明,组织形成和维持受到细胞-细胞和细胞-基质相互作用之间的差异机械信号的调节,这反过来又引起差异收缩力和粘附,以确定细胞迁移和缔合的首选方向。
The ability of cells to form tissues represents one of the most fundamental issues in biology. However, it is unclear what triggers cells to adhere to one another in tissues and to migrate once a piece of tissue is planted on culture surfaces. Using substrates of identical chemical composition but different flexibility, we show that this process is controlled by substrate rigidity: on stiff substrates, cells migrate away from one another and spread on surfaces, whereas on soft substrates they merge to form tissue-like structures. Similar behavior was observed not only with fibroblastic and epithelial cell lines but also explants from neonatal rat hearts. Cell compaction on soft substrates involves a combination of weakened adhesions to the substrate and myosin II-dependent contractile forces that drive cells toward one another. Our results suggest that tissue formation and maintenance is regulated by differential mechanical signals between cell-cell and cell-substrate interactions, which in turn elicit differential contractile forces and adhesions to determine the preferred direction of cell migration and association.